Disclosures. Management of Chronic, Non- Terminal Pain. Learning Objectives. Outline. Drug Schedules. Applicable State Laws

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Disclosures Management of Chronic, Non- Terminal Pain No financial disclosures or conflicts of interest to report Michael A. Smith, PharmD, BCPS Clinical Assistant Professor, University of Michigan College of Pharmacy Pain and Palliative Care Clinical Pharmacy Specialist, Michigan Medicine Objectives Review Applicable state laws Osteoarthritis Low back pain Neuropathies Cases Outline Learning Objectives Describe the role of opioid, non-opioid, and adjuvant analgesics in the management of chronic, non-terminal pain syndromes Recommend specific treatment modalities given a patient case Applicable State Laws Effective December 2016: Registered nurses who hold a specialty certification (nurse practitioner/nurse midwife) MAY: Prescribe controlled substances in schedules II-V under the supervision of a physician Prescribe controlled substances in schedule II regardless of location of practice Limited to no more than a 30 day supply Drug Schedules Schedule II Opioids*, marijuana** Schedules III IV Benzodiazepines, ketamine, tramadol, pregabalin Board of Medicine. Rule 338.2411. (Page 7) 1

Pain Pain Processing Unpleasant sensory and emotional response associated with actual or potential tissue damage Acute occurs suddenly, short-lived, resolves as acute illness resolves Inflammation and transduction Conduction Transmission Modulation Perception Chronic lasts longer than expected healing process (or > 3 months), affects ADLs www.iasp-pain.org/terms-p.html http://www.painfoundation.org/learn/publications/files/painresourceguide2009.pdf Pathogenesis Goals of Chronic Pain Management Visceral Nociceptive Somatic Central Neuropathic Peripheral Keep patient functional Improve mental health Decrease pain perception and dependence on drug therapy Decrease rate of physical deterioration Reduce pain as much as possible without undue adverse effects Assessment of Pain Thorough patient history CC, HPI, ROS, PMH Validated pain scales (visual analog scales) Physical exam Imaging and diagnostic studies Assessment of Pain P what Provokes the pain? Q Quality of the pain? R does the pain Radiate? S Severity of the pain? T Time of the pain? 2

Non-Pharmacologic Therapy Pharmacologic Therapy Physical/Occupational therapy Transcutaneous electrical nerve stimulation Psychotherapy Cold/heat Massage Prayer/meditation/spiritual Distraction Exercise Music Gordon. Healthcare. 2016;4 (2): 22. Jauregui. Surg Tech Int. 2016; 28:296-302. World Health Organization Analgesic Ladder Pharmacologic Options Mechanistic Approach Acetaminophen NSAIDs Muscle relaxants TCAs SSRIs, SNRIs Gabapentinoids Anticonvulsants Anti-arrhythmics Lidocaine Capsaicin Cannabinoids Opioids Ketamine Corticosteroids Bisphosphonates Peripheral Nociceptive Neuropathic Centralized NSAIDs X X Opioids X Surgery/Injections X TCAs SNRIs Gabapentinoids X Cannabinoid X Osteoarthritis JS is a 68 year old female who endorses bilateral knee pain Liver cirrhosis (secondary to NASH) T2DM Asthma Osteoarthritis Acetaminophen NSAIDs Topical therapies Intra-articular injections How do you want to treat? 3

Acetaminophen NSAIDs Centrally acting analgesic and anti-pyretic Inhibits COX-2 enzymes in CNS Other possible mechanisms: cannabinoid receptor activation, nitric oxide production inhibition, substance P inhibition, serotonergic/opioid pathway modulation Analgesic, anti-inflammatory, anti-pyretic Inhibits COX enzymes COX-1 (normal tissue) vs. COX-2 (inflammation) Generally very well tolerated Hepatotoxicity seen with acute and/or chronic use Herndon. Pharmacother. 2008; 28(6):788-805. NSAID Adverse Effects Gastrointestinal GI upset, GI bleeding Cardiovascular HF, MI, HTN Hepatic Renal Acetaminophen vs NSAIDs Osteoarthritis Hands topical or oral NSAIDs Hips acetaminophen, NSAIDs Knees the above plus intraarticular injections Hochberg. Arthritis Care Res. 2012; 64 (4): 465-74. Acetaminophen vs NSAIDs Acetaminophen vs NSAIDs da Costa. Lancet. 2016; 387: 2093-105. da Costa. Lancet. 2016; 387: 2093-105. 4

Osteoarthritis JS is a 68 year old female who endorses bilateral knee pain Liver cirrhosis (secondary to NASH) T2DM Asthma Patient received: topical diclofenac, transdermal fentanyl, and tramadol Low Back Pain OB is a 60 year old female presenting for routine follow-up HIV Vision loss (secondary to cortical stroke) Chronic low back pain T2DM Depression How do you want to treat? Acetaminophen NSAIDs Muscle relaxants Low Back Pain Acetaminophen vs NSAIDs Low back pain Acute likely prefer NSAIDs New guidelines recommend NSAIDs or muscle relaxants Chronic patient preference New guidelines recommend NSAIDs (1 st ), then either tramadol (2 nd ) or duloxetine (2 nd ) Saragiotto. Cochrane Library. 2016; Issue 6. Art. No.: CD012230. Enthoven. Cochrane Library. 2016; Issue 2. Art. No.: CD012087. Muscle Relaxants Can reduce acute low back pain up to ~30% Use with caution in patients with fall risks Should not be used for chronic back pain or those with injury unrelated to muscles No data exists regarding chronic back pain Muscle Relaxants Dose (mg) Avoid Notes Cyclobenzaprine 5-10 TID Heart Methocarbamol 750 QID MG Carisoprodol 350 QID AIP CIV Chlorzoxazone 250-750 TID-QID Liver Metaxalone 800 TID-QID Liver Orphenadrine 100 BID MG; Elderly Tizanidine 4 TID-QID Heart Baclofen 5-20 TID Renal dose Abdel Shaheed. Eur J Pain. 2016; Epub Ahead of Print. 5

Low Back Pain OB is a 60 year old female presenting for routine follow-up HIV, vision loss, chronic low back pain, T2DM, depression Patient was receiving: Oxycodone ER 80 mg TID + oxycodone IR 5 mg Q6H PRN CDC Guidelines No studies > 1 year of opioid vs. placebo, etc. Most studies 6 weeks in duration Long-term opioid use is associated with an increased risk of opioid abuse or dependence Risk of opioid abuse or dependence increases with: History of substance abuse, younger age, major depression, psychotropic medication use Risk of overdose increases above 50 oral morphine equivalents (OME) MMWR. Vol 65. No.1. CDC Recommendations Non-pharmacologic therapy and non-opioid therapy are first line Only use opioids if benefits outweigh risks and continue to use non-pharmacologic and nonopioid based therapies Establish treatment goals before opioid use Frequently re-evaluate and re-educate CDC Recommendations Use immediate release formulations Use the lowest dose necessary Re-assess benefits if exceeding 50 OME for total daily dose (TDD) Avoid increases above 90 OME TDD Long-term use often starts with treating an acute pain episode Prescribe no more than is reasonably necessary for that condition MMWR. Vol 65. No.1. MMWR. Vol 65. No.1. CDC Recommendations Evaluate patients 1 to 4 weeks after starting opioids and at least every 3 months thereafter Consider mitigating strategies like narcotic contracts, naloxone co-prescriptions, prescription drug monitoring program checks, urine drug screens, avoid benzodiazepine coprescriptions, and consider referral for opioid use disorders as needed ACP Guidelines on Low Back Pain Acute non-drug therapy first, then NSAIDs Chronic non-drug therapy first, NSAIDs (1 st ), tramadol (2 nd ), duloxetine (2 nd ) Only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients MMWR. Vol 65. No.1. Qaseem. Ann Intern Med. 2017. 6

Neuropathic Pain JS is a 47 year old female complaining of worsening pain Hypothyroidism Hypertension T1DM ESRD on HD (MWF) Peripheral arterial disease OSA on CPAP How do you want to treat? Neuropathic Pain Beydoun. J Pain Symptom Manage.. 2003;25:S18-30. Treatment Options Drug CV Renal Liver Notes Amitriptyline X Sedating, ACh Nortriptyline X Orthostasis Imipramine X Sedating, ACh Duloxetine X X Venlafaxine Caution Caution Caution Headaches, low = SSRI Gabapentin Caution Renal dosing Pregabalin Caution Renal dosing Carbamazepine Caution Caution Caution Drug interactions Lamotrigine Caution Caution Renal/Hepatic dosing Opioids No morphine Extend tramadol frequency Lidocaine X Consider smaller areas of treatment Treatment Options Drug Initial Dose (mg) Target Dose (mg) Maximum Daily Dose (mg) Amitriptyline 25 QHS 100 QHS 150 Nortriptyline 25 QDay 100 QDay 150 Imipramine 25 QHS 100 QHS 150 Duloxetine 30 QDay 60 QDay 60 Venlafaxine 75 QDay 150-225 QDay 225 Gabapentin 300 QDay 1800 TDD 3600 Pregabalin 50 TID 100 TID 600 Carbamazepine 200 QDay 400-800 QDay 1200 Lamotrigine 25 QDay 200-400 QDay 600 Opioids LOWEST LOWEST LOWEST Lidocaine One patch - Three patches Neuropathic Pain JS is a 47 year old female complaining of worsening pain Hypothyroidism, hypertension, T1DM, ESRD on HD (MWF), peripheral arterial disease, OSA on CPAP Monitoring Onset of analgesic effect Duration of analgesic effect PRN medication use Adverse drug effects of medications Concomitant medication use Patient was receiving: Amitriptyline, gabapentin, oxycodone/acetaminophen 7

Management of Chronic, Non- Terminal Pain Michael A. Smith, PharmD, BCPS Clinical Assistant Professor, University of Michigan College of Pharmacy Pain and Palliative Care Clinical Pharmacy Specialist, Michigan Medicine 8